This project is principally directed at determining the fate of injected insulin in normal and insulin-immunized animals. To this end, guinea pigs will be immunized with insulin, insulin derivatives such as the "A" component, and with homologous and heterologous islets. Tissues from these animals will be studied histologically to define lesions which may be induced in the pancreas, kidneys, and elsewhere; and to detect tissues which might contain insulin-antibody complexes. The immunized animals themselves will be used to determine the fate of injected insulin and factors which might modify that fate. In other studies, the fates of insulin and (hopefully) glucagon will be examined in vitro in the presence of hepatocytes.